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I. Perlman, E. Zemel, S. Soudry, A. Loewenstein; The Developing Mammalian Retina Is Protected From Gentamycin Toxicity. Invest. Ophthalmol. Vis. Sci. 2008;49(13):3880.
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In the developing mammalian retina, the photoreceptors outer segments continuously elongate as a result of high level of outer segment disc synthesis and low level of shedding. The purpose of this study was to investigate whether the developing mammalian retina is more resistant to toxic insults in comparison with the adult retina.
Gentamycin, an aminoglycoside antibiotic highly toxic to the retina was injected to the right eyes of newborn rabbits, aged 11-30 days and to adult rabbits. The left eye of each rabbit was injected with saline and thus served as its own control. Dark- and light-adapted electroretinogram (ERG) responses were recorded 8 weeks after injection. For each rabbit, the b-waves of both eyes were plotted as a function of log flash intensity, and the intensity-response curve was fitted to a Michaelis-Menten type function in order to derive Vmax, the maximum response amplitude, andσ, the semi-saturation constant. The ratio between Vmax values (experimental eye/control eye) was used to asses the degree of drug toxicity. After 8 weeks the rabbits were sacrificed, and the retinas were prepared for histopathological studies at the light microscopic level and for GFAP immunocytochemistry.
The ERG recordings demonstrated practically no damage in rabbits injected at postnatal age of 11 and 13 days, and a gradually increasing severity of functional retinal damage with increasing postnatal age of intravitreal injection, up to a severe functional deficit of the retina in the experimental eye of the adult rabbit. The histopathological studies yielded similar results, where no retinal damage could be observed in the retinas of rabbits injected at postnatal age of 11 and 13 days, and a gradually increasing severity of retinal damage in rabbits injected at older postnatal ages. Retinas showing functional and structural damage also exhibited GFAP expression in the Muller cells.
The electroretinographical and morphological findings show that the developing mammalian retina is partially protected against toxic drugs. The younger the rabbit at time of exposure to the toxic drug, the less sever is the permanent damage. these findings suggest that the process of outer segment renewal may provide the means for recovery from toxic damage to the outer segments.
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